前列腺癌分子探针68Ga-DOTA-ANCP-PSMA的初步评价

Preliminary Evaluation of Prostate Cancer Molecular Probe 68 Ga-DOTA-ANCP-PSMA

前列腺癌是男性最常见的恶性肿瘤,前列腺癌总体的病死率达到11%。前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)是前列腺癌诊断的理想靶点,68 Ga标记的PSMA小分子抑制剂可用于前列腺癌诊断、分期和疗效评价,68 Ga-PSMA小分子抑制剂已成为国际研究的热点。为研发一种新型的具有较好体内性质的68 Ga标记的PSMA小分子化合物,以谷氨酸-脲-赖氨酸为核心、1,4,7,10-四氮杂环十二烷-1,4,7,10-四羧酸(DOTA)为螯合剂,设计了新型的PSMA小分子抑制剂68 Ga-DOTA-ANCP-PSMA,前体化合物采用固相合成法合成,再使用68 Ga直接标记,然后测定了标记物的体内外性质。在优化的标记条件下,标记率可达95%以上。纯化后的标记物在磷酸缓冲液体系下和血清蛋白体系下2 h的体外稳定性较好,脂水分配系数为-1.42。生物分布研究显示:68 Ga-DOTA-ANCP-PSMA在血液清除较快,主要通过肾脏代谢,肝脏的放射性摄取较低,在心脏、肺、脾等非靶器官中的放射性摄取均较低,由于标记物主要通过尿液排泄,膀胱显示出较高的摄取值,在肿瘤部位也有明显摄取。在正电子发射断层扫描(PET)-计算机断层扫描(CT)的研究中,68 Ga-DOTA-ANCP-PSMA分子探针在肿瘤位置有清晰的影像,显示出较好的灵敏度和特异性。该化合物体内外性质较好,有较好的研究和开发前景。

Prostate cancer is the most common malignant tumor in males with high mortality.The mortality rate is over 11%.Prostate specific membrane antigen(PSMA)is an ideal target for prostate cancer diagnosis.Using positron emitter 68 Ga labeled PSMA small molecule inhibitors for prostate cancer diagnosis,staging and efficacy evaluation has become a world-wide focus.In order to develop a new 68 Ga labeled PSMA probe with better properties both in vitro and in vivo,a novel PSMA small molecule inhibitor 68 Ga-DOTA-ANCP-PSMA was designed.The precursor compound was synthesized by peptide solid phase synthesis.68 Ga was labeled to the PSMA probe directly.The labeled compound properties both in vitro and in vivo were measured.The purified labeled compound shows good stability in vitro.Radiochemical purity can be stable in PBS and BSA system for 2 hours.The octanol-water partition coefficient is-1.42.Biological distribution studies show fast blood clearance,low liver uptake,and renal metabolism.There are low uptake in non-target organs such as the heart,lung and spleen.Bladder shows a high uptake,because the labeled compound mainly excrets through urine.Tumor shows high uptake.In the PET-CT imaging study,68 Ga-DOTA-ANCP-PSMA is clear imaging in tumor,also shows good sensitivity and specificity in PET-CT block study.This compound has good properties in vitro and in vivo.It may have good research and development prospect for prostate cancer diagnosis.